系列硬质胆囊镜的研发

中国医生提出的硬镜微创保胆取石（息肉）新概念,对于治疗胆囊结石和胆囊息肉取得较好的临床效果。目前国内外没有专门针对胆囊病手术所设计的内镜设备。专门为胆囊病手术的发展而研发的系列硬质胆囊镜及其配套附件,已经获得多项国家专利授权,并成功在国家认定的药物临床试验机构中应用手术120多例。     

60Co-γ射线辐射诱变蝴蝶兰M1代花型突变体的RAPD分析

利用72个10bp随机引物对蝴蝶兰（F141780）及其60Co-γ射线辐射的8个表现型花型突变体进行RAPD分析。其中有30个引物能扩增出理想的带型,有4个随机引物扩增出的带型显示其中的25-6、304、30—8-2等3个突变体与对照品种之间具有稳定的多态性差异,即初定其为基因型花型突变体。     

Fluorescence emission mechanism and fluorescence properties of ternary Tb(III) complex with diphenyl sulphoxide and bipyridine

A novel ternary complex, TbL₅L′(ClO₄)₃·3H₂O, two binary complexes, TbL₇(ClO₄)₃·3H₂O and TbL′_3.5(ClO₄)₃·4H₂O has been synthesized (using diphenyl sulphoxide as the first ligand L, bipyridine as the second ligand L′). Their composition was analysed by element analysis, coordination titration, IR spectra and ¹H‐NMR, and the fluorescence emission mechanism, fluorescence intensities and phosphorescence spectra were also investigated by comparison. It was shown that the ternary rare‐earth complex showed stronger fluorescence intensities than the binary rare‐earth complexes in such material. The strongest characteristic fluorescence emission intensity of the ternary system was 8.23 times, 3.58 times as strong as that of the binary systems TbL₇(ClO₄)₃·3H₂O and TbL′_3.5 (ClO₄)₃·4H₂O, respectively. By fluorescence analysis it was found that both diphenyl sulphoxide and bipyridine could sensitize the fluorescence intensities of rare‐earth ions. In particular, in the ternary rare‐earth complex, introduction of bipyridine was of benefit to the fluorescence properties of Tb(III). Copyright © 2011 John Wiley & Sons, Ltd.     

Bacterial niche-specific genome expansion is coupled with highly frequent gene disruptions in deep-sea sediments

The complexity and dynamics of microbial metagenomes may be evaluated by genome size, gene duplication and the disruption rate between lineages. In this study, we pyrosequenced the metagenomes of microbes obtained from the brine and sediment of a deep-sea brine pool in the Red Sea to explore the possible genomic adaptations of the microbes in response to environmental changes. The microbes from the brine and sediments (both surface and deep layers) of the Atlantis II Deep brine pool had similar communities whereas the effective genome size varied from 7.4 Mb in the brine to more than 9 Mb in the sediment. This genome expansion in the sediment samples was due to gene duplication as evidenced by enrichment of the homologs. The duplicated genes were highly disrupted, on average by 47.6% and 70% for the surface and deep layers of the Atlantis II Deep sediment samples, respectively. The disruptive effects appeared to be mainly due to point mutations and frameshifts. In contrast, the homologs from the Atlantis II Deep brine sample were highly conserved and they maintained relatively small copy numbers. Likely, the adaptation of the microbes in the sediments was coupled with pseudogenizations and possibly functional diversifications of the paralogs in the expanded genomes. The maintenance of the pseudogenes in the large genomes is discussed.     

Safety evaluation of DT388IL3, a diphtheria toxin/interleukin 3 fusion protein, in the cynomolgus monkey

We developed a fusion toxin, DT₃₈₈IL3, consisting of the catalytic and translocation domains of diphtheria toxin (DT₃₈₈) linked to interleukin 3 (IL3) for the treatment of patients with acute myeloid leukemia (AML). Our goal in this study was to estimate a range for the maximum tolerated dose (MTD) and to evaluate the dose-limiting toxicity (DLT) of DT₃₈₈IL3 in cynomolgus monkeys (Macaca fasicularis), which possess cross-reactive IL3 receptors. In our previous study, we administered up to six infusions of DT₃₈₈IL3 at 40, 60, or 100 g/kg every other day to three pairs (one male monkey and one female monkey) of young adult monkeys. In five of six monkeys, results showed a dose-dependent increase in malaise and anorexia but no consistent abnormalities in serum chemistries or blood counts. There was no evidence of organ damage by blood tests or histopathology. However, the female treated at 100 g/kg, died of moderate to severe vasculitis of multiple tissues. Based on these findings, this study repeated the 100 g/kg group and added a group that received 150 g/kg in an effort to confirm a dose response. Two female monkeys were treated with up to six infusions of DT₃₈₈IL3 at 100 g/kg or 150 g/kg every other day. One additional female monkey was treated as a negative control. Monkeys in the 100 g/kg group showed moderate malaise and anorexia, but no consistent abnormalities in blood counts or serum chemistries. Moderate elevations of liver enzymes were noted in the 150 g/kg group in addition to severe malaise and anorexia. No significant findings were revealed at gross necropsy. The histopathological findings revealed regenerative myeloid hyperplasia and hepatic degeneration and regeneration in the 150 g/kg group. Similar lesions of less severity were detected in the 100 g/kg group. DT₃₈₈IL3 plasma half-life was approximately 20 min with a peak concentration of approximately 2 g/ml (30,000 pM). The IC₅₀ for AML blasts in vitro was 6 pM. Collectively, our results suggest that DT₃₈₈IL3 can be tolerated at doses up to 100 g/kg in a nonhuman primate, which is higher than previously reported for other AML directed diphtheria toxin fusion proteins, and should in principle allow for dose escalation with reduced toxic side effects. Based on these findings a phase I clinical trial has recently been initiated with DT₃₈₈IL3 for the treatment of AML.     

Global human genetics of HIV-1 infection and China

Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.     

The N-terminus of Drosophila ESC mediates its phosphorylation and dimerization

The ESC protein, like other Polycomb Group proteins, is required for heritable silencing of the homeotic genes. ESC is phosphorylated in vivo, but the region of ESC that is phosphorylated and its consequences are not known. Here, we show that the amino-terminal region of ESC (residues 1-60) mediates its phosphorylation and dimerization. Phosphorylation of ESC1-60 in vitro by CK1 and CK2 strongly enhances its dimerization. Both phosphorylation and dimerization are conserved in the mammalian ESC homolog EED, suggesting that they play important roles in vivo. One role is suggested by the effect of phosphatase treatment on native ESC complexes, which does not affect the integrity of the 600 kDa ESC/E(Z) complex, but eliminates the 1 MDa ESC/E(Z) complex, which is distinguished from the former by the presence of the additional subunits PCL and RPD3. Thus, stability and perhaps assembly of larger ESC complexes may depend on ESC phosphorylation.